title: Effects of amiodarone, thyroid hormones and CYP2C9 and VKORC1 polymorphisms on warfarin metabolism: a review of the literature.
abstract: OBJECTIVE
  To review the literature regarding the interaction among amiodarone therapy, thyroid hormone levels, and warfarin metabolism.
  
  
  METHODS
  A 73-year-old male with type 2 after describing an unusual case of amiodarone-induced thyrotoxicosis (AIT) who experienced a severe rise in international normalized ratio (INR) values after initiating warfarin therapy due to an unusual combination of excessive thyroid hormones, amiodarone therapy, and a genetic abnormality affecting warfarin metabolism.
  
  
  RESULTS
  Genetic analysis revealed that the patient was CYP2C9*2 wild-type, CYP2C9*3/*3 homozygous mutant, and VKORC1*3/*3 homozygous mutant. A review of the literature revealed that both mutations can independently affect warfarin metabolism. In addition, amiodarone therapy and the presence of thyrotoxicosis per se can affect warfarin metabolism and reduce the dose needed to maintain INR in the therapeutic range. The association of the 2 genetic polymorphisms in a patient with AIT is extremely rare and strongly impairs warfarin metabolism, exposing the patient to a high risk of overtreatment.
  
  
  CONCLUSIONS
  In patients with AIT, warfarin therapy should be gradually introduced, starting with a very low dose, because of the significant risk of warfarin overtreatment. Whether the genetic analysis of CYP2C9 and VKORC1 polymorphisms should be routinely performed in AIT patients remains conjectural.
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Tomisti
authors.forename: Marzia
authors.initials: M
authors.lastname: Del Re
authors.forename: Luigi
authors.initials: L
authors.lastname: Bartalena
authors.forename: Maria L
authors.initials: ML
authors.lastname: Tanda
authors.forename: Angelo
authors.initials: A
authors.lastname: Pucci
authors.forename: Franco
authors.initials: F
authors.lastname: Pambianco
authors.forename: Romano
authors.initials: R
authors.lastname: Danesi
authors.forename: Lewis E
authors.initials: LE
authors.lastname: Braverman
authors.forename: Enio
authors.initials: E
authors.lastname: Martino
authors.forename: Fausto
authors.initials: F
authors.lastname: Bogazzi
mesh_terms: D000368:Aged; D000638:Amiodarone / Q000009:adverse effects*; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D000925:Anticoagulants / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D004247:DNA / Q000235:genetics; D004347:Drug Interactions; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D012306:Risk; D013963:Thyroid Hormones / Q000009:adverse effects* / Q000097:blood; D013965:Thyroidectomy; D013971:Thyrotoxicosis / Q000139:chemically induced / Q000378:metabolism / Q000601:surgery; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D014859:Warfarin / Q000378:metabolism*
chemical_list: D000889:Anti-Arrhythmia Agents; D000925:Anticoagulants; D013963:Thyroid Hormones; D014859:Warfarin; D004247:DNA; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases; D000638:Amiodarone